Mealey KL, Burke NS. Assessment of verdinexor as a canine P-glycoprotein substrate. J Vet Pharmacol Ther. 2023. doi:10.1111/jvp.13123
P-glycoprotein (P-gp) substrate status of antineoplastic drugs is important because neoplastic cells that express P-gp can actively efflux P-gp substrates, negatively impacting the drug’s efficacy. In addition, chemotherapeutic drugs generally have a narrow therapeutic index; thus, chemotherapeutics that are P-gp substrates can cause severe adverse reactions in patients with P-gp dysfunction (eg, dogs with multidrug sensitivity gene [MDR1] mutation [also known as ABCB1-1delta], cats with ABCB11930_1931del TC).
In this study,* a canine kidney cell line induced to overexpress canine P-gp was used to assess the P-gp substrate status of verdinexor, an antineoplastic drug FDA-approved for the treatment of canine lymphoma. Based on a cytotoxicity assay and a competitive flow cytometry assay, the study demonstrated verdinexor is not a substrate for canine P-gp. Dogs affected by the MDR1 mutation or with unknown MDR1 status can thus be given verdinexor at labeled doses for treatment of lymphoma.
*This study was funded by Anivive.
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